JI6

JI6 is a potent, selective and orally active FLT3 inhibitor, with IC₅₀s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits JAK3 and c-Kit, with IC₅₀s of ∼250 and ∼500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia^[1]. In Vitro:JI6 (3-1000 nM; 1-4 days) selectively inhibits the viability of MV4-11 cells in a dose-dependent manner, with an IC₅₀ of ∼25 nM^[1].
JI6 (1-2000 nM; 48 h) potently inhibits the viability of HCD-57 cells expressing FLT3-ITD, FLT3-D835Y, and FLT3-D835H with IC₅₀s of ∼40 nM, but it displays essentially no effects on the parent HCD-57 or the cells transformed with JAK2V617F^[1].
JI6 (100-500 nM; 24 h) induces apoptosis and cell cycle arrest in both FLT3-ITD- and FLT3-D835Y-expressing HCD-57 cells^[1].
JI6 (50-500 nM; 3 h) inhibits phosphorylation of FLT3 and its downstream signaling transducers including ERK and Akt in FLT3-ITD- and FLT3-D835Y-transfromed HCD-57 cells^[1]. In Vivo:JI6 (15 mg/kg; i.p. daily for 3 weeks) inhibits the proliferation of FLT3-D835Y-transformed HCD-57 in immunodeficient mice and prolongs the mice survival^[1].
JI6 (25 mg/kg; p.o. daily for 3 weeks) suppresses myeloproliferative phenotypes in FLT3-ITD knock-in mice^[1].
JI6 (100 mg/kg; a single i.p.) significantly inhibits phosphorylation of FLT3 and downstream signal transductionin mice expressing FLT3-D835Y^[1].